CV Data Shows No Benefit, Risk to GLP-1 Receptor Agonist Lixisenatide

July 6, 2015

A large phase IIIb study showed no increased risk for cardiovascular problems with GLP-1 receptor agonist lixisenatide.

Use of the glucagon-like peptide (GLP)-1 receptor agonist lixisenatide among people with type 2 diabetes had a neutral effects on heart failure and other cardiovascular problems, providing no additional benefit or creating no additional risk, according to the results of the ELIXA trial presented at the American Diabetes Association's 75th Scientific Sessions.

"There has been a cloud of suspicion over all new diabetes drugs, including GLP-1 agonists, over whether they may increase the risk for cardiovascular problems," Marc Pfeffer, MD, PhD, Dzau Professor of Medicine at Harvard Medical, Senior Physician in Cardiology at Brigham and Women's Hospital and Principal Investigator for the ELIXA trial, said. "This is the first report of a clinical trial designed to assess cardiovascular outcomes in this class of drugs and we have shown that patients and their healthcare providers should have no cause for concern, even if they are at high risk for heart-related problems."

The large phase IIIb study compared outcomes among 6,068 people from 49 countries. Patients were randomly assigned to treatment with lixisenatide or placebo and then followed for more than 2 years.

Lixisenatide was found to be non-inferior to placebo for the composite primary endpoint of major cardiovascular events that included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina (HR=1.017; 95% CI, 0.886-1.168).  However, lixisenatide failed to prove superiority compared with placebo.

An analysis of cardiovascular safety endpoints showed that lixisenatide resulted in no increased risk for heart failure (HR=0.96) compared with placebo. In addition, patients assigned to lixisenatide were no more likely than those assigned to placebo to experience hypoglycemia, pancreatic cancer, pancreatitis, malignancy, or drug-related allergic reactions.

Lixisenatide is a once daily injectable drug currently on the market in Europe, Japan, Australia and Mexico. The drug manufacturer, Sanofi, plans to resubmit a drug application for lixisenatide to the FDA in the third quarter of 2015.

“Knowing these drugs can be prescribed safely gives physicians another tool to further lower glucose without producing more hypoglycemia, a potential complication of improved glycemic control,” Eldrin Lewis, MD MPH, Associate Professor of Medicine, Harvard Medical School, Advanced Heart Disease section of Cardiovascular Division at Brigham and Women's Hospital, said. “These drugs can provide a very important adjunct to therapy. We want to get people to target to minimize the future consequences of diabetes, but we don't want to add any additional risks in doing so.”

Reference: Pfeffer MA, et al. The evaluation of lixisenatide in acute coronary syndrome-the results of the ELIXA trial. Symposium at the 75th Scientific Sessions of the American Diabetes Association; Boston, MA; June 8, 2015. http://www.diabetes.org/newsroom/press-releases/2015/elixa.html